Process for the manufacture of carotenoids and intermediates therefor



United States Patent PROCESS FOR THE MANUFACTURE OF CARO- TENOIDS AND INTERP/[EDIATES THEREFOR Otto Isler, Marc Montavon, and Rudolf Ruegg, Basel,

and Paul Zeller, Neuallschwil, Switzerland, assignors .1 to Holimann-La Roche Inc., Nutley, N. J., a corporation of New Jersey No Drawing. Application August 23, 1956 1 Serial No. 605,717

, I Claims priority, application Switzerland August 31, 1955 I 20 Claims. (Cl. 260-488) on, em

' vention may be broadly described was'comprising thefol- A 3,8-dimethyl-2,9-di-loweralkoxy 1,3,5,7,9-decapentaene; or a 3,8 dimethyl-2,9-di-lower-' alkoxy-l,3,7,9-decatetraen-5-yne (referred to for con-' 2,857,423 H Patented 2 1, 19%8 The overall process encompassed by the present inlowing procedure.

venience as dienol ethers) is condensed bilaterally with a C -acetal of the type characterized hereinafter, (i. e.

one molecule of dienol ether with two molecules of C acetal). The 'c -hexaalkoxy-compound obtained as a condensation product is treated, with acid to produce a C -6,l3-diketone which, in turn, is reduced to the'cor-l responding C -6,l3-diol. The C -6,'13-diol thusobtained is subjected to dehydration, splitting oif two molecules of water and undergoing concomitant allyl rearrangement, to

obtain the C -carotenoids described above. If desired, the

6,13-diol may be esterified prior to the final dehydration.

Where a 3,8 dimethyl 2,9-di-loweralkoxy-1,3,7,9 decatetraen-S-yne is used as one of the initial reactants, a 15,15'- dehydro carotenoid is obtained as the product. This maybe partially hydrogenated on the triple bond and isomerized to obtain the same end product as obtained by the use of a 3,8-dimethyl-2,9-di-loweralkoxy-1,3,5,7,9-decapentaene initially.

The process may be represented by the following flo diagram in which the synthesis leading to B-carotene is; used as illustrative (R representing a lower alkyl radical):

CH1 CH3 CHa I on, on,

CH3 CH Ha R Ha CH; CH

. if on H3 CH3 r I 1 7 C C C -acetalswhich. maybe. initially condensedbilaterally with one of the dienol ethersreferred to above, are 1,1- di-loweralkoxy-2-methyl-4-R-2-butenes wherein R represents zaimemben ofzthet-groupzconsistingr10f the radicals R l-cyclohexem l yl, 2,6;6E-trin1ethyl-1,3-cyclohexadienr- 1-yl=v andi 2,6,6trimethyl-5-hexene1-ylidene;. wherein R represents; a memberiof the :groupsconsisting of hydrogen, x0; hydroxyiandiacyloxy and R representsazmember of the griouprconsisting rofhydrogen, hydroxy. and acyloxy. Representative. acyl groupsarei-aliphatioalkanoyl groups suchyas acetyl on palmiloyl: Illustrative examplesof the .G aeetals which; be. used starting; materials in the process. of this invention (and'the final product which maybe. obtained when that acetali is condensed with 'hexen 1 yl) 2 methyl 2 2 butene (zeaxanthin),

1,1 diethoxy 4 (2,6,6- trimethyl 4 hydroxy 1- cycloh'exylidene)-2-methyl-2-butenev (zeaxanthin) 1,1- diethoxy 4 4 (2,6,6 trimethyl- 4 hydroxy 1' -cyclohexen l yl) 2 methyl 2 buten'e (zeaxanthin), 1,1- diethoxy 4' (2,6,6 trimethyl 5 hexen 1 ylidene) 2-methyl-2-butene (lycopene), etc.

When a 3,8-dimethyl-2,9-di-loweralkoxy-1,3,7l9-decatetraen-S-yne is condensed bilaterally with the C -acetals enumerated above, the respective l5,15'-dehydro analogs.

of the final.products indicated are then obtained.

The preferred dienol" others used as starting materials for'the present process are. 3,8f-dimethyl 2,9 diethoxy The end products obtained according to the method of this invention are useful as coloring agents for foodstufis, e. g. butter, cheese and margarine, and for feeds'tufis, imparting a yellow-orange color. B-carotene, 3,4-3,4-bisdehydro-lS-carotene, also possess the biological activity characteristic of vitamin A.

In the first stage of a detailed: procedure accordingto and 3,8.-dimethyl-2,9-diethoxythe present invention; a dienol ether oftlie clas'scharact'e'r ized above is condensed bilaterally-in the presence of an acid condensation agent with a C -acetal of the class described above. As condensation agents for the first step of the process there may be used metal halide acid condensation agents such as boron trifluoride etherate, zinc. chloride, titanium tetrachloride, ferric chloride, tin tetrachloride, etc. lowest possible reaction temperature in. order to avoid undesirable side reactions such as polymerization. optimal. reaction temperatures lie between 15 and 50, depending on the choice of condensation agent and the starting materials used.

According to a preferred modification, one mol of dienol ether and two mols of C -acetal are reacted at 20 The condensation is efiected at the.

to 40 in an inert solvent such as petroleum ether in the presence of zinc chloride or boron trifluoride etherate. The solution containing the condensation product thus obtained is preferably subjected to hydrolysis without isolation or purification. If '3',8-diniethyl-2,9=di lower alkoxy-l,3,7,9-decatetraen-5-yne is condensed with a C acetal, there is obtained as the product of the first step, a 1,18 di R 3,7,12,16 tetramethyl 4,6,6,13,13,l5-

water.

hexa loweralkoxy 2,7,11,16 octadecatetraen 9 yne,

wherein R corresponds to the configuration of the C acetal starting material as defined above. When 3,8-

dimethyl 2,9 di loweralkoxy 1,3,5,7,9 decapentaene V is condensed with a C -acetal, thei -product of the first step isa 1,18 di R 3,7,12,16- tetramethyl 4,6,6,13,13,15- hexa-loweralkoxy-2,7,9,1 1,16-octadecapentaene. wherein R corresponds to the configuration of the C -acetal starting material as defined above.- The reactionproductof? the first stagebfthis process need notnbe isolated. If-desired, the second hydrolysis step ofthe processzmay-be carried out in the same reaction vessel.

The second stage of'they-process.constituteshydrolysis of the reaction productobtained in the first stage. The

hydrolysis may be carriedouhqfor example, by Warming the reaction mixture obtained previously, whereby two mols of alcohol are simultaneously split off from the 4,5

andlh. 15,,positionsand a.6,l3:di t0ne i ..fornie HY:

drolysismaybe etie'ctedintlie pre ence f wa er. solub e- 1 organic or inorganic. acids. such, as p-toluenesulienic. cid;

acetic. acid, propionic acid; oxalic acid, sulfuric acidfland; phosphoric; acidior in the. presence. of l,aci'd reacting, water. -1 solublenietal salts such .as zinc. chloride or sodiumbishl; fate. Preferably oxygenis excludedtrom the reaction,"

and. an antioxidant such as hydroquinone. is added... Thereaction is. preferably carried: out under conditions. in

which the. alcohol produced is continuously. removedlirom. the. reaction mixture. A watenmiscible. solventsuch as.

dioxane, tetrahydrofurane,ethylenegiycol dimethylrethere; etc., may be added in order to obtain a homogeneous reaction mixture. The condensation, product is preferably warmed to about with dilute phosphoric acid in the 6,13-diketone produced precipitates out.

chromatography and by' crystallization.

octadecahexaen 9 yne 6,13 diones or 1,18 di R 3,7,12,16 tetramethyl 2,4;7,9,11,14,l6 octadecaheptaene 6,13 -diones wherein R has the same significance as discussed above.

In the third stage of the process, the 6,13-diketone obtained above is reduced to the corresponding 6,13-diol, e. g. 1,18 di R 3,7,12,16 tetramethyl 2,4,7,ll,l4,l6-

octadecahexaen. 9 yne 6,13 'diol or 1,18 di R 3,7,12,16 tetramethyl- 2,,4;,7,9,11,14,16 octadecaheptaene-6,13-diol, R having the same significance as above. This: is:- effected, for example, by treating the diketone with an alkali metal hydride reducing agent such as sodium or lithiumborohydride or with sodium or lithium aluminum hydride in a solvent. When substituents in the nature of alcohols or esters are present, an excess of the reducing agent is preferably utilized. A preferred modification comprises stirring the 6,13-diketone .in an inert solvent with sodium borohydride or With'lithium' aluminum hydride and after hydrolysis of the reaction product, extracting with ether the 6,13-diol which has 'been formed. 7

Alternatively, the reductionof the 6,13-diketone to the 6,13-diol can be efiected by treating the 6,13-diketone with an aluminum alcoholate, such as aluminum is-opropylatec In a preferred modificatiomthe 6,13-diketone is treated with aluminum isopropylate and isopropanol-in an inert solvent, such as benzene, continuously removing from' the reaction mixture the acetone formed. V 7

Depending. on the reaction conditions, oxo and acyloxy. groups-'whichmay be present in the 4-position of the ring can be reduced or saponified.

The 6, 13-diols produced are hard resins or crystalline,

substances which display characteristic absorption maxima in the ultraviolet spectrum. They are prefer- A preferred modification comprises treating a solution of the 6,13- diol or a lower alkanoic acid ester thereof in an inert solvent such as ether, methylene chloride, di oxane, etc., with water-free hydrohalic acid, e. g. hydrochloric acid. It is advantageous to work in ethyl ether,

and to use an excess of alcoholic hydrochloric acid; A small amount of acid is sufficient if the reaction is accelerated by heating.

Another preferred modification comprises treating the 6,13-diol or a lower alkyl ester thereof in a halogenated hydrocarbon with a large dipole moment at a temperature below 0 with aqueous hydrohalic acid. Water or a basic compound is then used to split off hydrogen halide from the halogenated compound produced. Methylene chloride or chloroform may be used as solvents and concentrated aqueous hydrobromic acid may be used as an aqueous hydrohalic acid.

B-Garotene, 3,4-3,4'-bisdehydro-fi-carotene, zeaxanthin, lycopene or their l5,15-dehydro analogs are thereupon obtained as a product depending upon the initial starting materials as described above. For example, from l,l8-di-(2,6,6-trimethyl-l-cyclohexen-l-yl)- or 1,18-di- (2,6,6-trimethyl-l -cyclohexylidene) -3 ,7,12,16-tetramethyl- 2,4,7,l1,14,16-octadecahexaen-9-yne-6,13-diol ortheir esters, there is obtained l5,l5'-dehydro-,5'-carotene; from 1,18-di-(2,6,6-trirnethyl-l-cyclohexen-l-yl)- or 1,18-di- (2,6,6-trimethyl-1-cyclohexylidene)-3,7,12,16-tetramethyl- 2,4,7,9,11,14,16-octadecaheptaene-6,13-diol there is obtained fi-carotene; from 1,18-di-(2,6,6-trimethyl-1-cyclohexen-1-yl)- or 1,18-di-(2,6,6-trimethyl-l-cyclohexylidene) 3,7,12,16 tetramethyl 2,4,7,11,14,16 octadecahexaen-9-yne-6,l3-diol substituted in the 4-position of both rings, or esters thereof, there are obtained 15,15- dehydrozeaxanthin or esters thereof; from 1,18-di-(2,6,6- trimethyl-l-cyclohexen-l-yl)- or 1,18-di-(2,6,6-trimethyll cyclohexylidene) 3,7,12,16 tetramethyl 2,4,7,9,11- 14,16-octadecaheptaene-6,13-diol substituted in the 4-position of both rings, or esters thereof, there are obtained zeaxanthin or esters thereof; from 1,l8-di-(2,6,6-trimethyl- 1,3 cyclohexadien-1-yl)-3,7,12,16-tetramethyl 2,4,7,1-1,-

14,16-octadecahexaen-9-yne-6,l3-diol or esters thereof.

there is obtained 3,4-3,4-l5,15-tris-dehydro-13-carotene; from l,18-di-(2,6,6-trimethyl-1,3-cyclohexadien-l-yl)3, 7,12,16 tetramethyl 2,4,7,9,11,14,16 octadecaheptaene-6,l3-diol or esters thereof there is obtained 3,4- 3',4 bis dehydro )3 carotene; from 1,18-di (2,6,6trimethyl 5 hexen l ylidene) 3,7,12,16 tetram ethyl- 2,4,7,11,14,l6-octadecahexaen-9-yne-6,13-diol or esters thereof there is obtained 15,15'-dehydrolycopene and from 1,18-di-(2,6,6-trimethyl-5-hexen-l-ylidene)-3 ,7,12, 16 tetramethyl -'2,4,7,9,11,l4,l6 octadecaheptaene- 6,13-diol, or esters thereof, there is obtained lycopene.

The 'l5,15'-dehydro compounds may be converted into their corresponding non-acetylenic analogs by partial hydrogenation of the triple bond by means of a leadpalladium-calcium carbonate catalyst in an inert solvent, such as petroleum ether or acetic acid ethyl ester, and then isomerizing by heating a suspension of the hydrogenated product for several hours at 80100 C. in a solvent such as benzene or petroleum ether.

Certain dienol ethers and C -acetals utilized as starting materials for the process of the present invention are novel. The preparation of the dienol ethers is exemplitied at the end of Examples 1 and 2. The synthesis of some C acet als is described below:;

138 'g. of 2,6,6-trimethyl-1 cyclohexen-4-one [which can bemade, for example, from isophorone by known procedures, compare Kharasch, Journal of the American Chemical Society, 63 2308 1941)] in 50 ml. of glacial acetic acid were stirred for'two hours at 010 with 160 ml. of'per'acetic acid (containing 530 mg. of peracetic'acid per ml.) and the mixture was allowed to stand overnight at 20. Then, while adding ice, the reaction mixture was made weakly alkaline (pH about 8) by adding 30% aqueous NaOH solution, and the reaction mixture was shaken for one hour at 20 Then the mixture was extracted twice, each time with 800 mlof diethyl ether, and the ether solutions were washed once .with 200 ml. of saturated ammonium chloride solution. The ether solutions were combined and dried over sodium sulfate, the solvent was driven off, and the residue was distilled in high vacuum. A forerun passed over between 70 and and then 2,6,6-trirnethyl-2-cyclohexen-.

l-ol-4-one was obtained as an almost colorless oil hav mum at 226 m (E}=11l0 in petroleum ether solution) after standing for some time. The phenylsemicarbazone had M. P. 189-190", U. V. maxima at 240.5 mg and 285 (E=807 and 778 in ethanol) To 154 g. of 2,6,6-trimethyl-2-cyclohexen-l-ol-4-one in 200 ml. of glacial acetic acid and 500 ml. of water were in a second separatory funnel with 500 ml. of petroleum ether. The petroleum ether solutions were washed with saturated ammonium chloride solution to which a little ammonia had been added, and then with pure saturated ammonium chloride solution. The washed extracts were dried over' sodium sulfate and the solvent was driven off.

The product, 2,6,6-trimethyl-2-cyclohexene-1,4-dione, was distilled under a water pump vacuum; B. P. 92-

94/11 mm., a yellow oil which solidified to crystalline form in the refrigerator, n =1,490, U. V. maximum at 238 mp.

(Ei=942 in petroleum ether) The phenylsemicarbazone had M. P. 190, then resolidified and melted again at 230, U. V. maxima at 242.5 m and 325.5 m

( 1=s75 and 580 in ethanol) 65 g. of 2,6,6-trimethyl-2-cyclohexene-1,4-dione in 250 ml. of glacial acetic acid were slowly reacted with g. of zinc dust, while stirring, so that the temperature did not rise above 50". Then the reaction mixture was stirred for an additional period of one hour. The reaction mixture Was filtered, diluted with 1000 ml. of water and then saturated with ammonium chloride. The mixture was extracted twice, each time with 800 ml. of petroleum ether (boiling range 30-60"). The petroleum ether solutions were Washed with 300 ml. of saturated ammonium chloride solution to which some ammonia was added, and

then were washed with pure saturated ammonium chlo ride solution. (In case a portion of the product crystallizes from the petroleum ether solution, it is filtered off,

the crystalline material is dissolved in diethyl ether, then the diethyl ether solution is washed 'as indicatedabove, dried over sodium sulfate and then combined with the petroleum ether solution.) The solvent was dri ven off until the product 2,6,6-trimethyl-1,4-cyclohexanedione started to crystallize out; colorless needles, M. P.63-6S',

having no. absorption maxirnum in the ultraviolet speci .washed with diethyl ether: and added tothe filtrate.

trum between 220 and 280 mi. The pheny1-semicarba- .zonehadiM; P. 2l8 -220 U. V; maximum at 250 mu.

(Bi lO30-in ethanol) e To a-lithium amide. suspension prepared by dissolving 6.7 g. oflithiuminZDOO mLof-liquid, ammonia was added slowly, while, stirring, 52 g. of l-methoxy-2-methyl-3- but-yn-Zeol. The. mixture was stirred, for one hour and then 79." g. of 2,6,6-trimethyl-4rethylenedioxy-l-cyclohexanone. were added, and the reaction mixture was-stirred overnight at the boiling temperature of the ammonia. 60 g. of ammonium chloride were added and then the ammonia was driven off. The residue was taken up in diethyl ether, and insoluble material was filtered oh; the ether solution was washed witha saturated solution of ammonium chloride, then was dried over sodium sulfate, and the ether was driven off. The residue was suspended in- 450 ml. of petroleum ether and was extracted four times, each time with 300 ml. of 70% methanol. The methanolextracts were washed three times, each time with 150 ml; ofpetroleurn ether, then were diluted with saturated an'unonium chloride solution and the precipitated material-was taken up in diethyl ether. The ether solution was washed with water, dried over sodium sulfate, and the ether was driven 01f; There were thus obtained 92 g. of 4- (2,6,6 trimethylA-ethylenedioxy-l-hydroxy-1- cyc1ohexyl).-2-methyl-l-methoxy-3-butyn-2-ol as a yellow Viscous oil,

, 92 g. ofi the latter were dissolved in 3000 ml. of dry diethyl ether, were mixed while stirring at 5 with a solution of 22.5 g. of lithium aluminum hydride in 300 ml. of dry diethyl ether, and the reaction mixture was refluxed for four hours. Then the reaction mixture was cooled with ice, 250. ml. of methanol were added slowly while stirring at, 0-51, and; the clear solution was poured intoa mixture of 100g. of ice and 6.00 ml..of saturated.

ammonium chloride solution. The precipitated aluminum hydroxide was filtered oif and the precipitate was The combinedv liquors were washedwith Water, dried over dium: u fa e. ans t e. ol n s e d i n 01 T residue was partitioned between petroleum ether and 70% methanol, in the manner indicated above, and from the methanol extracts there were obtained 70 g. of 4-(2,6,6- trimethyli -.4- ethylenedioxy l' hydro-xy 1 cyclohexyl):-.2+methyl-l-methoxy13abuten-2aol as a lightyellow, viscousoil;

7tl:g.; of the-latter weremixedwith 140- ml. of formic acidzand the mixture'was heated for minutes at 100. The reaction. mixture was. pouredonto ice and extracted with cliethyliether, the ethreal solution was washed with water and withdilute sodium bicarbonate solution, dried ovensodium sulfate-,and' theether was driven off. The residue-was dissolved in 200 ml. of glacial acetic acid, 26 ml; of water andB'Q: gof sodiumacetate were added, and the.=,mixture: wastheated, at 95 for two hours. Then it wasdilutedzwith ice water, and was. extracted with diethyl ether; the; etherextract wag washedwith water and with dilute, sodiumbicarbonate solution, dried over sodium sulfate 3Bl;.ii.i$.i.hl': was driven off. The residue was ilistilled'imvacuum, thereby yielding 4-.(2,6,'6-trimethyl ffoxoylrcyclohexylid'ene)-2-methyl-2-buten-1-al as a yel- 0 L.vimaxim raatzwmu inv Petroleum h haY gB. P; ca. TIN/002mm; n =1.555'

hexylidene.):2:methyl-2 buten-l-al in- 34; m1. of either.-

formicacidethyl ester and 7 m1; oflabsolute-ethanol was.

mixed-with 0.65 ml. of: orthophosphoric acid and; 0.05 g. ofpetoluenesulfonic acid,v audithemixture was allowed; 7 of r to stand for; 24 hours. at; room. temperature. pyridine were added and then, the mixturewas, poured p n i e and'dilute sodium ic r on ol n. he re.

sulting. mixture was extracted with petroleum ether, the; petroleum ether extract was washed with water, dr edi oversodium;v sulfate, the solvent-was driven off and the;

residue was dried in vacuo at 60. There were thus ob-. tained ,40 g.. of 4-(2,6,6 trimethyl-4-oxo-l-cyclohexyl;,

idene)-2-methyl-Ll-diethoXy-Z-butene (U. V. maximum at 24.8 m tinthepetroleum ether). i

40 g. ofthe latter product were dissolved in 600ml.

of dry diethyl ether and weremixed slowly, while stirring.

at O5, with a solution of 2.8 g. of lithium aluminum hydride in 40 ml. of diethyl ether. Thereaction mixture 7 was stirred for one hour at room temperature, thenwas cooled to 0-5"; 20 ml. of methanol were added slowly,

and the reaction, mixture was poured upon ice and: satu:

rated ammonium chloride solution. The precipitated.

aluminum hydroxide Was'filtered 0E and washedwithdi:

ethyl ether, the ether was added to the. filtrate, the com,- bined liquors were dried over sodium sulfate and the.

solvent material was. driven off; There were. obtained.

39.5 g. of 4-(2,6,6-trimethyl-4-hydroxy-lrcyclohexylt idcne -2-methyll ,1-diethoxy-2-butene.

39.5 g. of the latter were acetylated by mixing it with 40 ml. of pyridine and 20 ml. of acetic anhydride and permitting the mixture to stand. for 20 hours. The re;

action mixture-was poured into ice water, extracted with petroleum ether, the organic layer was. washed with;

cold sodium bicarbonate solution, dried over sodium. sulfate and the solvent was driven off, yielding. 42 g.of 1

4.- (2,6,6 trimethyl 4.- acetoxy 1 cyclohexylidene) Z-methyl-1,1-diethoxyr2-butene.

42 g. ofthe latter were mixed with 400 ml. of glacial acetic acid, 50 ml. of water and 65 g. of sodium acetate and heated at for three hoursf Then the reaction mixture was.v diluted with ice water and was extracted; The ethereal solution was washed with diethyl ether. several times with water, dried over sodium sulfate and the ether was driven off. There were thus obtained-3l= g. of 4-(2,6,6-trimethyl-4-acetoxy-l-cyclohexylidene)-2- methyl-2-buten-l-al (U. V. maximum at 284' my in petroleum-ether) V 3 1 g. of 4-. (2,6,6 trimethyl-4-acetoxy-l-cyclohexylk dene)-2-rnethyl-2-buten-l-al were dissolved in 40 ml. of toluene, mixed with 16 g. of isopropenyl acetate and 0.2 g. of p-toluenesulfonic acid and the mixture was heated at -140 while continuously removing the ace- 7 tone which was formed. After approximately two hours, the reactionmixture was cooled down, poured into ice water and extracted with petroleum ether. The

petroleum ether solution was washed with cold sodium bicarbonate solution and then with water, dried over 7' sodium sulfate and the solvent was distilled off. There were thus obtained 34 g, of 4-(2,6,6-trimethyl-4-acetoxy- 1 cyclohexen l yl) 2 methyl 1 acetoxy 1,3

butadiene (U. V. maximum at 262 m in petroleum ether).

34g. of the latter were dissolved in 750 ml. of meth--. anol, mixed with 75 ml. of Water and 27 g. of sodium bicarbonate and the mixture was refluxed for six hours while stirring. Then the reaction mixture was diluted' with ice water, extracted with diethyl ether, the ether solution was washed with water, dried over sodium sulf fate and the ether was driven off. In order to insure acetylation of the nuclear hydroxy group, the residue,'. '7 presumably containing at least some erase-sim an.

4 hydroxy -.1 cyclohexen 1, yl) 2- methyl '2 buten-l-al, was mixed with 60 ml; of pyridine and ml. of acetic-anhydride and the mixturewas allowed to stand for 20 hours 'at roomtemperature. -1-00'rnl-.*=ofwater, dried over sodium sulfate ice water were added and the mixture was then extracted with diethyl ether. The ethereal solution was washed with cold sodium bicarbonate solution and then with and the solvent was driven off. a

7.3 g. of the 4-(2,6,6-trimethyl-4-acetoxy-1-cyclohexen-l-yl)-2-methyl-2-buten-1-al thus obtained were dis: solved in 6.8 ml. of ethyl ortho-formate and there was added a solution of 0.13 ml. of orthophosphoric acid in 1.3 ml. of absolute ethanol; After addition of 0.005 g. of p-toluenesulfonic acid, the reaction mixture was allowed to stand at room temperature for 24 hours. Then 1.5 m1. of pyridine were added and the mixture was poured into a mixture of 100 g. of sodium bicarbonate solution and 20 g. of ice. The product was taken up in ether, the ether extract washed with sodium bicarbonate and water and dried .over sodium sulfate.

' After evaporation of the solvent there was obtained the 1,1 diethoxy 4 (2,6,6 trimethyl 4 acetoxy 1 cyclohexen 1 yl)-2-methyl-2-butene. From this compound the 1,1-diethoxy-4-(2,6,6-trimethyl-4-hydroxy-1- stirred 18 hours at room temperature. The solvent was distilled off in vacuo. To the 1,l8-di-(2,6,6-trimethyl-1- cyclohexen 1 yl) 3,7,12,16 tetramethyl 4,6,6,13,13,

cyclohexen-l-yl)-2-methyl-2-butene may be prepared by v boiling the' former with sodium bicarbonate in 90% aqueous methanol. 1,1 diethoxy 4-(2,6,6-trimethyl-4- acetoxy-l-cyclohexen-1-yl)-2-methyl-2-butene may be obtained from the latter by treating at 20 with acetic anhydn'de in the presence of excess pyridine.

1,1 diethoxy 4 (2,6,6 trimethyl 1 cyclohexylidene)-2-methyl-2-butene, which is a further starting material in this process, can be prepared as follows:

To 250 ml. of dry liquid ammonia were added 50 mg. of ferric nitrate and a few minutes later, while.

stirring, 50 mg. of lithium. Dry air was blown into the blue solution for one minute. were added slowly and awaited after each addition until the blue color of the solution disappeared. Thereupon, 18.75 g. of fi-chlorovinyl-ethyl-ether were added while stirring well, and 10 minutes later, 17 g. of 2,6,6-trimethyl-cyclohexanone was dropped in slowly. The mixture was stirred for -44 hours, then slowly reacted with 22.5 g. of ammonium chloride and finally the ammonia was allowed to evaporate. 400 ml. of diethyl ether were then added and the mixture was filtered. The ethereal solution was dried over sodium sulfate, concentrated and the residue was distilled. The distillate was dissolved in 115 ml. of high boiling petroleum ether and shaken with 5 g. of lead-poisoned palladium catalyst in a hydrogen atmosphere at room temperature until the hydrogen uptake ceased. The catalyst was filtered ofi, the petroleum ether solution was concentrated and the residue was shaken for 1% hours at room temperature with a mixture of 100 ml. of dioxane, 17.5 ml. of 3 N-sulfuric acid and 7.5 m1. of water. Thereupon the mixture was diluted with water, the product was taken up in petroleum ether and the petroleum ether solution was washed with dilute sodium bicarbonate solution and water, dried over sodium sulfate and concentrated. Upon distillation of the residue there were obtained 8.5 g. of 2,6,6-trimethyl-1-cyclohexylidene acetaldehyde. The latter was acetalized by reaction with orthoformic acid triethyl ester in the presence of p-toluenesulfonic acid, thereby forming 2,6,6-trimethyl-cyclohexylidene 'acetaldehyde diethyl acetal. The latter was condensed with ethyl-propenyl ether in the presence of zinc chloride thereby forming 4 (2,6,6 -t1imethyl-1-cyclohexylidene) -2-methyl-1,1,3-triethoxy-butane. Upon hydrolysis-dialcoholation of the latter by heating with acetic acid and sodium acetate to 100, 4-(2,6,6-trimethyl-1- cyclohexylidene) -2-methyl-2-buten-1-al was formed. This compound was acetalized as described above with orthoformic acid ethyl ester in the presence of p-toluenesulfonic acid; U. V. absorption maxima at 247.5 m in petroleum ether.

' The following examples are illustrative of the present invention.

Then, 2.05 g. of lithium 15 hexa ethoxy 2,7,11,16 octadecatetraen 9 yne thus obtained were added 10 ml. of dioxane, 27 ml. of 90% acetic acid and 4 g. of sodium acetate and the mixture was heated 5 hours while stirring at 95, whereby the 7 reaction product slowly began to crystallize. The still warm reaction mixture was diluted with 10 m1. of water and permitted to crystallize at 0-5". The yellow crystals were filtered under suction, washed with water and dried.

The crude 1,18 di (2,6,6 trimethyl 1 cyclohexen 1- yl) 3,7,12,16 tetramethyl 2,4,7,11,14,16 octadecahexaen-9-yne-6,l3-dione was purified by recrystallization from methylene chloride-methanol, M. P. 168-170; U. V. maxima at 257 and 344 m in petroleum ether.

One g. of 1,18 di 2,6,6 trimethyl 1 cyclohexen- 1 yl) 3,7,12,16- tetramethyl 2 ,4,7,l1,14,16 octadecahexaen-9-yne-6,13-dione in ml. of dry ether gradually was treated with a'solution of 0.075 g. of lithium aluminum hydride in 15 ml. of dry ether while stirring at about 50 and then stirred at room temperature for one hour. The reaction mixture was then poured over a mixture of 20 g. of ice and 20 ml. of 3 N-sulfuric acid, the organic layer was separated, washed with water and dilute sodium bicarbonate solution, dried over sodium sulfate and evaporated. There was obtained 1 g. of .1,18-di- (2,6,6 trimethyl 1 cycl-ohexen 1 yl) 3,7,12,16- tetramethyl 2,4,7,11,14,16 octadecahexaen 9 yne- 6,13-diol as a yellowish resin, which became crystalline on standing (U. V. absorption maxima at 242 and 282 my in petroleum ether).

The diol obtained above was directly converted without further purification by dissolving in 20 ml. of ether, treating with 2 ml. of 23.7% alcoholic hydrochloric acid and 4 ml. of alcohol. The solution was left standing at room temperature for 2 hours and an additional 18 hours at 0 to 5". The crystals which formed were then filtered under suction, washed with methanol and petroleum ether and dried. The l5,l5'-dehydro- 3-carotene obtained melted at 154-155 (U. V. maxima at 431 and 457 m in petroleum ether). v

The 3,8 dimethyl 2,9 diethoxy 1,3,7,9 decatetraen-S-yne used as a starting material was prepared as follows:

A solution of 162 g. of 2,7-dimethyl-2,6-octadien-4-yne- 1,8-dial in 1600 ml. of absolute diethyl ether was treated with 250 g. of methyl magnesium bromide. The condensation product was hydrolyzed and 3,8-dimethyl-2,9- dihydroxy-3,7-decadien-S-yne was obtained. g. of 3,8 dimethyl 2,9 dihydroxy 3,7 decatrien 5 yne were shaken for 15 hours in methylene chloride solution with 1500 g. of manganese dioxide. 45 g. of 3,8-dimethyl-2,9-dioxo-2,7-decadien-5-yne thus produced were suspended in 65 ml. of orthoformic acid ethyl ester. After addition of a solution of 0.08 g.of p-toluenesulfonic acid in 8 ml. of ethanol, the mixture was stirred for 48 hours at room temperature.

33.8 g. of the acetal'formed were then heated in a toluene soluu'on at 100 for 2 hours with 15.3 g. of phosphorus oxychloride in the presence of excess pyridine. The 3,8 dimethyl 2,9 diethoxy 1,1-1,7,9 decatetraen- 5-yne formed showed U. V. absorption maxima at 320 and 340 m, (in petroleum ether). 7

Example 2 scribed in Example l-with l'ml. of a zinc chlorideethyl acetate solution 4 g. of 3,8-dimethy l-2,9-diethoxy 4 1,3,5,7,9 decapentaene (U. V. maxima at 320, 334 and 350 In in petroleum ether) in 10 ml. of benzene. The 1,18 di (2,6,6 trimethyl 1 cyclohexen 1 yl)- 3,7,12,16 tetramethyl 4 4,6,6,'13,13,15 hexa ethoxy' 2,7 ,9,11,16 octadecapentaene thus obtained was then hydrolyzed with ml. of dioxane, ml. of 90% acetic acid and 8 g. of sodium acetate. The 1,18 di (2,6,6- trimethyl 1 cyclohexen l yl) 3,7,12,16 tetramethyl 2,4,7,9,11,14,16 octadecaheptaene 6,13 dione was purified by crystallization from methylene chloridemethanol, M. P. 178 '(U. V. maxima at 256 and 359 m l in petroleum ether). U V

Qne g. of 1,18 di (2,6,6 trimethyl 1 cyclohexen- 1 f yl) 3,7,12,16 tetran' le thyl 2,4 ,7,9,1l,l 4,16 octadecahept aene-6,l3-dione was reduced as described in Example 1 with 0.075 g. of lithium aluminum hydride and similarly worked trimethyl 1 cyclohexen 1 yl) 3,7,12,16 tetramethyl 2,4,7,9,11,14,l6 octadecahept aene 6,13 diol (U. V. absorption maxima at 242 and 294 m in petroleum ether). Without further purification the product thus obtained was dehydrated with alcoholic hydrochloric acid in ether solution as described in Example 1. There was obtained {i -carotene, MQP. 180 (U. V. maxima at 452 45,3 and 480481 m in petroleum ether).

The 3,8 dimethyl 2,9 diethoxy 1,3,5,7,9 decapentaene required as a starting compound was prepared in the following manner from 3,8-dimethyl-2,9-diethoxy- 1,3,7,9- decatetraen-5-yne [the synthesis of which is described at the end of Example 1]:

6 g. of 3,8 dimethyl 2,9 diethoxy 1,3,7,9 decatetraen-S-yne were dissolved in 90 ml. of petroleum ether (boiling range 80100). The solution was then shaken at room temperature with 1 g. of lead-palladium catalyst (Lindlan Helv. Chim. Acta 35, 446 [1952] and 0.1 ml. quiuoline in a hydrogen atmosphere. After 1 mol of hydrogen was taken up, tion and the petroleum ether solution was washed with cold dilute sulfuric acid and with water, dried over sodium sulfate and the solvent was driven off. The3,8-dimethyl- 2,9 diethoxy 1,3,5,7,9 decapentaene can be recrystallized from petroleum ether; U.'V. absorption maxima at 3 20, 334 and 350 m (in petroleum ether solution). x m l 3 4.2 -g. of 1,1-diethoxy-4-(2,6,6-trimethyl-4-oxo-cyclohexylidene)-2-rriethyl-2-butene were dissolved in 5 ml. of

dry petroleum ether and condensed as described in Example l 'with0.5 ml. of zinc chloride-ethyl acetate solution and 1.8 g. 'of 3,8-dimethyl-2,9-diethoxy-1,3,7,9- decatetraen-S-yne in 10 ml. of dry petroleum ether. The

product was then hydrolyzed with 10 ml. of dioxane, 27

ml. of 90% acetic acid and 4 g. of sodium acetate for 5 hoursat 95. The, reaction solution was then diluted with water and extracted with ether-methylene chloride (4:1). The ether solution was washed with water and sodium bicarbonate solution, dried over sodium sulfate and evaporated. There was obtained 1,18-di-(2,6,6-tri- 'methyl-4-oxo-1-cyclohexylidene)-3 ,7,12,16-tetramethyl-2, 4,7,11,14,16-octadecahexaen-9-yne-6,13-dione which was purified by chromatography (U. V. absorption'maxima at 258, 292-293 and 368 m in petroleum ether).

3.3 V g. of 1,18-di-(2,6,6-trimethyl-4-oxo-l-cyelohexylidene) 3,7,12,16 -tetramethyl 1 2,4,7,11,14,16 octadecahexaen-9-yne- 6,13-dione in 50 ml. of dry ether were redu ced as described in Example 1 with 0.4 g. of lithium aluminum hydride and similarly worked up. There was obtained 1 1 S-di- 2,6,6-trimethyl-4-hydroxy-1-cyclohexylidene) 3,7,12,16 tetramethyl 2,4,7,11,14,16 octeidecahexaen-9-yne-6,l3-diol as a yellowish resin (U. V. absorption maximum at 292 my. in petroleum ether).

The product obtained above was dissolved .in 10 m1. of

up. There was obtained 1,18 -di-(2,6,6-

the catalyst was separated by filtra- 12 Ra sins asat sl w th mlat ase is a d d a d l t tead f r 29 119M511} r9921 warts-ma ts u der t o en atais rhst T sastis llifill? w then d ut d w t 59 s 99 W te ttracte wit et er the ether 9 1 tion was washed with cold 1 N-hydrochloric acid, with 915 s l ts sq i m bisarheaate $9 3 Q d t Wat rie QYe cetacetas Obta nd ,-t mt yl id ene)-3,7,12,16-tetrameth I l-;6 ,13-

ether).-

The anqsii q obtai ed.

was de rat it o t u ifies tion b issa n i 5 mlfof glacial acetic acid. The solution was treated with 1 11s are -4 under vigorousstirring;

s t b mis sa With n 0 eco ds at were a d dand the mixture was stirred for an additional n ca b n diox a spher The 3 1 9 F Qr m hy en chl ride sa u oa w h n s a a ed. ashed washed 3 times with water, driedover sodium sulfate an tamer,- Il s studs P d F s d wa hmi matog'ra bed on aluminum oxide (Broclgmann, activity.

state I l) he 15 ,l5 -dehydro-zeaxanthin thus obtained was eluted with a mixture of equal, parts of methylene ttl -us abate-manna. M- r- .8? (U. SQm- U el t 4 9 a 58 m n trol um ether) m le 4 8.6 g. of 1,1-diethoxy-4-(2,6,6 trimethyll-acetoxy-1'- cyclohexen-l-yl)-2-methyl-2-butene were condensed asde scribed in Example 1 with-0l75 ml. of 'zinc chloride-ethyl acetate solution and 3.5 g. of 3,8-dimethyl-2,9 diethoxy- 1,3,7, 9-decatetraen-S-yne, then hydrolyzed'as described in Example'3 with 14 ml. of dioxane, 40 ml. of acetic acid and 6 g. of sodium acetate and then worked up as described in the same example. The crude 1,18-di-(2,6,6- trimethyl-4-acetoxy-l-cyclohexen 1 yl) 3,7,12,16-tetra (U. V. maxtma at 256 and 244 m obtained was reduced with lithiuma-luminum hydride without further purification as-d'eseribed in Example '3. The crude l',l8-di-')i2,6,-

6-triniethyl-4-hydfoxyl-cyclohexen- 1 -yl 3,7 1'2, 1 6 tetra methyl 2,4,7-,11,14,l6-octadecahexaen 9-yne-6,13-diol obtained was acetylated with acetic 'anhydridepyridin e, de-

hydrated with hydrobromic and saponified with alkali.

- Example. 5

, 131 ,g. of l l8 di-(2,6,6-trimethyl-l-cyclohexen l-yl)r 3,7,12,16 1- decamethyl -,2,4,7,11','14,16 4 octadecahexaenQ- yne -,6,'13 dione (the preparation of which is described in Example '1): were boiled with 131 g. of aluminum isoether. The .et e real solution was 'vvashed f3 times water, dried over sodium sulfate and the solv d iven fi- I cte. were 1 11. btain djfil o drum sulfate and the ether was then distilled ml. of methylene chloride and-1.8

, h mi e tron y agitated another 90 seconds at 35, 45 ml. of water sva ra e The esi e was sh r t sadntr s i e he and the purified y e rys: tallization from methylene chloride-petroleum ether and methyl-2,4,7,1 1,14,'l6-octadecahexaen-9 yne 6,13-dione acid in methylene chloride Following chromatography and crystallization fromfmethyle'n e chloride-petroleum; ether, 15,15 -dehydrozeaxanthin was obtained, MYP.

1 for 5 to 6 hours i s aircase-atusly distilling off. the acetone formed."

Example 7 6 14.5 g. of 1,18-di-(2,6,6-trimethyl-4-oxo-cyclohexylidene) 3,7,12,16 tetramethyl 2,4,7,11,14,16 octadecahexaen-9-yne-6,13-dione (prepared according to the procedure described in Example 3) were boiled for 5 to 6 hours in nitrogen atmosphere with 14 g. of aluminum isopropylate, 90 ml. of dry benzene and 200 ml. of dry isopropanol, continuously distilling off the acetone formed. The reaction mixture was cooled down and poured on a mixture of 50 ml. of 3-N-hydrochloric acid and 50 ml. of ice and was then extracted with diethyl ether. The ethereal solution was washed with water so as to show neutral reaction, was dried on sodium sulfate and the solvent was driven oif. There were thus obtained 14.8 g. of 1,18-di-(2,6,6-trimethyl-4hydroxy-cyclohexylidene) 3,7,12,16 tetramethyl 2,4,7,11,14,16 octadecahexaen-9-yne-6,13-diol which was directly used for the next step without further purification.

The diol obtained was dissolved in 150 ml. of diethyl ether and 30 ml. of ethanol. There were then added 15 m1. of 23.7% alcoholic hydrochloric acid and the mixture was allowed to stand for 3 hours at room temperature and for further 18 hours at 05. The crystals formed were separated by filtration and recrystallized from a mixture of ethyl acetate and methanol. There were thus obtained orange-red crystals of 15,15'-dehydrozeaxanthin; M. P. 207208.

Example 7 i or from a mixture of methylene chloride and methanol:

174-175 leum ether.

U. V. maxima at 254 and 343 me in petro- 5.2 g. of 1,18-di-l2,6,6-trimethyl-4-acetoxy-l-cyclohexen 1 yl) 3,7,12,16 tetramethyl 2,4,7,l1,14,16- octadecahexaen-9-yne-6,13-dione were reduced as described in Example 5 with 5.2g. of aluminum isopropylate in a benzene-isopropanol solution. The crude reaction product was then dehydrated without purification by dissolving in 100 ml. of methylene chloride and 3 ml. of glacial acetic acid. The solution was energetically stirred at -40 while adding within seconds 3.2 ml. of 60% hydrobromic acid. The mixture was agitated another 90 seconds at 100 ml. of water were added quickly and the mixture was stirred for an additional 3 hours. at, 05 in carbon dioxide atmosphere. After addition of 200 ml. of methylene chloride the organic layer was separated, washed with water, dried over sodium sulfate and the solvent was driven 01f. The crystalline residue was recrystallized from methylene chloride-methanol. There was thus obtained 15,15- dehydro-zeaxanthine of M. P. 207208; U. V. maxima at 430 and 458 m in petroleum ether.

Example 8 22.4 g. of 1,1 diethoxy 4 (2,6,6-trimethyl-1,3-cyclohexadien-l-yl)-2-methyl-2-butene were condensed with 9.8 g. of 3,8-dimethyl-2,9-diethoxy-1,3,7,9-decatetraen-5- yne and hydrolized with acetic acid and sodium acetate as described in Example 1. There were obtained yellow needles of 1,18 di-(2,6,6-trimethyl-1,3-cyclohexadien-1- yl) 3,7,12,16 tetramethyl 2,4,7,l1,14,16 octadecahexaen-9-yne-6,13-dioue which were recrystalized from methylene chloride-methanol, M. P. 153-154; U. V. maxima at 267 and 344 m (in petroleum ether solution).

4 g. of 1,18-di-(2,6,6-trimethyl-l,3-cyclohexadien-l-yl)- 3,7,12,16 tetramethyl 2,4,7,1l,14,16 octadecahexaen- 9-yne-6,13-dione were reduced as described in Example 5 with aluminum isopropylate in benzene-isopropanol solution and the 1,18-di-(2,6,6-trimethyl-1,3-cyclohexadien-1- yl) 3,7,12,16 tetramethyl 2,4,7,11,14,16 octadecahexaen-9-yne-6,13-diol obtained was dehydrated without purification with alcoholic hydrochloric acid in diethyl ether solution. After recrystallization of the product formed from methylene chloride-methanol, there were obtained red-violet crystals of 3,4-3',4'-15,15-trisdel1ydro-B-carotene, M. P. 165-l67; U. V. maximum at 449 m in petroleum ether solution.

We claim:

1. A process which comprises condensing bilaterally at 15 to C. in an inert solvent and in the presence of a metal halide acid condensation agent a member of the group consisting of 3,8-dimethyl-2,9-di-loweralkoxy-l,3,5,7,9-decapentaene and 3,8-dimethyl-2,9-diloweralkoxy-1,3,7,9-decatetraen-5-yne with 1,1-di-lower- 'cules of water are alkoxy-2-methyl-4-R-2-butene wherein R represents a member of the group consisting of the radicals 2,6,6-trimethyl-4-R -l-cyclohexylidene, 2,6,6-trimethy1-4-R l-cyclohexen-l-yl and 2,6,6-trimethyl-1,3-cyclohexadien-1-yl, said R representing a member of the group consisting of hydrogen, oxo, hydroxy and lower alkanoyloxy, and said R representing a member of the group consisting of hydrogen, hydroxy and lower alkanoyloxy, to produce a member of the group consisting of 1,18-di-R-3,7,12,16-

tetramethyl 4,6,6,13,l3,l5 hexa loweralkoxy 2,7,9, 11,16 octadecapentaene and 1,18 di-R-3,7,12,16-tetramethyl 4,6,6,13,13,15 hexa loweralkoxy 2,7,11,16- octadecatetraen-9-yne wherein R has the same significance defined above, hydrolyzing and dealcoholizing the product thus obtained in the presence of acid to produce a member of the group consisting of 1,18-di-R-3,7,12,16- tetramethyl 2,4,7,9,11,14,16 octadecaheptaene -'6,13- dione and 1,18-di-R-3,7,l2,16-tetramethyl-2,4,7,11,14,16- octadecahexaen-9-yne-6,13-dione, wherein R has the same significance defined above, catalytically reducing the 6,13- dione thus obtained to the corresponding 6,13-di01 and dehydrating the 6,13-diol with acid whereby two molesplit off with concomitant allyl re arrangement.

2. A process which comprises bilaterally condensing at 15 to 50 C. in an inert solvent and in the presence of a metal halide acid condensation agent 3,8-dimethyl-2,9-diethoxy-l,3,5,7,9-decapentaene with 1,1-diethoxy-4-(2,6,6, trimethyl 1 cyclohexen-l-yl)-2-methyl-2-butene to pro-- duce 1,18-di-(2,6,6-trimethyl l cyclohexen-l-yl)-3,7,12,

16 tetramethyl-4,6,6,l3,13,l5-heXaethoXy-2,7,9,l1,16-octadecapentaene, hydrolyzing and dealcoholizing the product thus obtained in the presence of acid to produce 1,18- di-(2,6,6-trimet hyl-l-cyclohexen 1 yl) 4 3,7,12,16-tetramethy1-2,4,7,9,1 1,14,l6-octadecaheptaene-6,13-dione, cat

alytioally reducing the 6,13-dione thus obtained to the corresponding 6,13-diol and treating the 6,13-diol with acid whereby two molecules of waterare split off with concomitant allyl rearrangementproducing ,B-carot'ene.

3. A process which comprises bilaterally condensing at 15 to 50 C. in an inert solvent and in the presence of a metal halide acid condensation agent 3,8-dirnethyl-2,9-diethoxy-1,3,7,9-decatetraen-5-yne with 1,1-diethoxy-4-(2,6, 6 trimethyl-4-oxo-l-cyclohexylidene)-2-methyl-2-butene to produce 1,18-di-(2,6,6 trimethyl-4-oxo-l-cyclohexylidene) 3,7,12,16 tetramethyl-4,6,6,13,l3,lS-hexaethoxy- 2,7,9,11,16-octadecapentaene, hydrolyzing and dealcoholizing the product thus obtained in the presence of acid to produce 1,18-di-(2,6,6-trimethyll oxo-l-cyclohexyli- L dene,),-3,7, 12, 16, tetramethyl-2,4,7:,1:1, 14,- laoctadecahex:

aen-9-yne-6,13-dione, catalyticallysreducing the 6,13-dione thus, obtained, esterifying. the productwitha lower; alkanoic acid andtreating the latter with acid; producing 1,5,15'-dehydrozeaxanthi n.

4 A process which comprises bilaterally condensing-at 15 'to 50 C. in an inert sol-yent-andin thepresence. of a metal halide acid condensation agent a;memberof the grouprconsisting of 3,8-dimethyl 2,9adi-loweralkoxy-1,3,5; 7,9-decapentaene and 3,8:dimethyl 2,9-di-loweralkoxy-1,3, 7,9-decatetraen-5-yne with 1,1-di-loweralkoxy-2-methyle4 R-Z-butene wherein R represents a member ofthe group Consisting of the radicals 2,6,6 -.trimethyl'-4-R -l-cyclohexyli dene, 2,6,6-trimethyl-4-R -l-cyclohexend-yl,and 2,6,6-,

,trimethyl-1,3-cycloheXadien-Lyl, said'R representing a;

octadecatetraen-9-yne wherein R represents a member uoi the group consistingof the radicals 2,6,6-trimethyl-4-R l-cyclohexylidene, 2,6,6-trimethyl-4-R -l-cyclohexen lryl and 2,6,6-trimethyl-1,3-cyclohe2radien-1-ylsaid R representing amember of the group consisting of hydrogen, oxo, hydroxy and lower alkanoyloxy, and said R repre; sentinga member of the group, consisting, ofhydrogen, hydroxy and lower alkanoyloxy, to produce. a member of the group consisting of 1,18-di-R-3,7 ;12,16-tetram ethyl- 2,4,7,9,11,14,16-octadecaheptaene-6,13-dione and 1,18-di- R-3,7,12,16 tetramethyl 2,4,7,11,14,16-octadecahexaen 9yne-6,13-dione wherein R has the same significance, defined above.

6. A. process which comprises catalytically reducing the 0x0 groups to hydroxy groups of amemberof the group consisting of 1,18-di-R3,7,12,16-tetramethyl 2,4,7,9,1l, 14,16-octadecaheptaen 6,13 dione; and 1,18 di;R-3,7',1 2', 16-tetramethyl-2,4,7 ,1 1,14,16-octadecaherraen 9 yne 7 6 13-dione wherein R is a member ot the groupconsisting of the radicals 2,6,6-trimethyl-4-R -Lcyclohegrylidene 2,6,

6-trimethyl-4-R -l-cyclohexen-l-yl and 2,6,6 tr irr et hyl;1,

3-cyclohexadien-1-yl, said R representing a member of the group consisting of hydrogen, oxo, hydroxy and lo wer alkanoyloxy, and said R representing a -member group consisting of hydrogen, hydroxy andlower alkanoyloxy.

7. A process which comprises treating a member of the group consisting of 1,18-di-R-3,7,12,16-tetramethyl-2,4,7, 9,11,14,16 octadecaheptaen-6,l3-dio1 and 1,18-di-R-3,'7, 12,16-tetramethyl-2,4,7,11,14,16-octadecahexaen 9 yne- 6,13-diol wherein R represents a member ofithe group consisting of the radicals 2,6,6-trimethy1-4-R -l-cyclohexylidene, 2,6,6-trimethyl-4-R -l-cyclohexen l-yl and 2,

6,6-trimethyl-1,3-cyclohexadien-1-yl, said R representing a member of the group consisting of hydrogen, hydroxy and lower alkanoyloxy, with acid whereby two molecules;

of water are split ofi with concomitant al 1y1 rearrangement.

f. he 7 8. A process which comprisesdehydrating 1,18-di- (2,6, 6-trimethyl-lacyclohexen layl) 3,7,12,16 tetramethyl-2,4, 7,9,1l,l4,16 octadecaheptaen-6,13rdiol with alcoholic hydrochloric acid to producefl-carotene.

octadecatetraen-9-yne wherein R represents a member of the group consisting-of the-radicals 2,6,6-trim'e thyl 4-R -1-cyclohexyl-idene, 2,6,6-trimethyl-4-R -l-cyclohexen-l-yl and 2,6,6-trimeth-yl 1 ,3 cyclohei adien-1-y1, said R representing a member of the; group consisting of hydrogen, oxo, hydrox y andloweralkanoy loxy, and-said R representing a member of the group consisting of hydrogen, hydroxy: and'lower alkanpyloxy: I 1

l4. A member of the group; consisting of 1,18-dl-R-I r et y 2 ;7; ;-1 4; J q d h p en- 6,13-dione and 1,18-di-R 3,7,12,16' tetramethyl-ZA-J,

11,14,16-octadecahexaen-9-yne-6,1 3-dione-whereinR represents a member of the -group consistingofthe radicals V 2,6,6-trimethyl-4-R -l cycloherylidene, 2,6 ,6-trimethyl-4e R -l -cyclohexen-l-yl and 2-,6=,6 -trimethyll,3-cycloheira dien-l-yl, said R representing a member of the. group;

consisting f' hydrogen, oxo, hy droxy' and lower alkanoyl oxy, andsaid R representing a-member of the group consisting of hydrogen, hydroxy andlower alkanoyloxy.

15. 1,18 di [2,6,6 trimethyl j- 1 cyclohexen-l-yll- 3,7,12,16 a et l ,1.6 c ade ah a 16. 1,18-di [2,6,6-trirnethyl 1,3 cyclohexadien-l -ylj- 3,7,12,16 tetramethylj 2 ,4,7,11,14,1 6' octadecahexafin- 9-yne-6,13-dione.

l7. 1,18-di-[2,6,6-trimethy1 4 acetoxy-1-cyclohexenl-yl] 13,112,1 6 tetramethyl- 2 ;4,711',l 4,16'- octadeca hexaen- 9.-yne-6,13-dione.

18. 1,18.-di-[2,6,6 trimethyl-A-oiro-l-cyclohexylidenel- I 3,7,12,16 tetramethyl 2, 4,'Z ;'11,14,16i-. octadecahexaen 9-yne-6,13 -dione.

19. 1,18-di [2,6,6 trimethyl 1,- cyclohexen-l-yll: 3,7,l2, 16 -.tetramethyl 2,4,7,9,l1,14,1,6 octadecaheptaen- 6,13-dione.

2Q. A member of the: group consisting ,of 'l,18 -d i-R- 3,7,12,16-tetramethyl 2,4,7,9,,11 ,14,16 octadecaheptaen; 6,13-diol and sentsa member of thegroup consisting Iofi the radicals 2,6,6-trimethyl-4-P-lacyclohfixylidene, 2,6,6-trimethyh4-Q R -l-cyclohexen -l yl and, 2,6,6-trimethy1-1,3rcyclohexaa: dien -1.-yl, said R representing amember of. the. group, consistingofi hydrogemlhydroxy and. lower alkanoyloxy. V

References Citedl in the file of; this patent UNI-TED :STATES PAIIE NIS,

2,609,396 "Inhoflen et a1; Sept. 2, 1952 2,671,112 Inhofienet'al- Mar.-2, 195,4 2,730,549.

9. 3,8-dimethyl-2,9-di-lowera koxy-1,3,5,7,9. decapenta 1,18-di-R- 3,7,12,l 6 tetramethyl-2,4,7,1 1, 14,16-octadecahexaen 9-yne-6,13-diol wherein; R' 116121.61.

Isler et: a1. Jan; 10, 1955 UNITED STATES PATENT OFFICE Certificate of Correction Patent No. 2,857,423 October 21, 1958 Otto Isler et al.

It is hereby certified that error appears in the printed specification of the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.

Column 1, line 24, for corotene read carotene; column 2, line 12, for C read 0 columns 1 and 2, first formula after the second plus sign, for

om cm (5H read 0H same columns 1 and 2, second. formula, for 0R in three occurrences, read 0R; column 3, lines 27 to 29, strike out 1,1-diethoxy-4- (2,6,6-trimethyl-4-acetoxy-l-cyclohexylidene) -2-methyl-2-butene(zeaxanthin); line 31, for methyl-2-2-butene read methyZ-Q-butene; column 4, line 54, for sodium, both occurrences, read s0dz'um-; column 5, line 46, for 3,7 read )-3,7; column 6, line 6, for 160 ml. read 160 9121.; same column 6, line 54, and column 7, line 3, after the closing parenthesis, in each occurrence, insert a period; column 7, line 61, for ethreal read ethereal; column 8, line 14, after in strike out the; column 10, line 5, for 3.8 read 3,8; line 25, for di2,6,6- read di- (2,6,6-; column 11, line 38, for 1952] and read 1952]) and; line 49, for ox0-cycloread 0w0-1-cy0Zo-; column 12, line 75, for trimethyl-cyclohexen read trimethyZ-I-cyclohemen; column 13, line 16, for 3-N read 3N; column 14, line 4, for recrystalized read recwstallized; column 15, line 49, for cyclohexylidene 2 read ayclohemylidene, 2.

Signed and sealed this 20th day of January 1959.

Attest= KARL H. AXLINE, ROBERT C. WATSON, Attesting Oficer. Gammz'ssioner of Patents. 

1. A PROCESS WHICH COMPRISES CONDENSING BILATERALLY AT 15 TO 50*C. IN AN INERT SOLVENT AND IN THE PRESENCE OF A METAL HALIDE ACID CONDENSATION AGENT A MEMBER OF THE GROUP CONSISTING OF 3,8-DIMETHYL-2,9-DI-LOWERALKOXY-1,3,5,7,9-DECAPENTAENE AND 3,8-DIMETHYL-2,9-DILOWERALKOXY-1,3,7,9-DECATETRAEN-5-YNE WITH 1,1-DI-LOWERALKOXY-2-METHYL-4-R-2-BUTENE WHEREIN R REPRESENTS A MEMEBER OF THE GROUP CONSISTING OF THE RADICALS 2,6,6-TRIMETHYL-1-4R1-1-CYCLOHEXYLIDENE, 2,6,6-TRIMETHYL-4-R2-1-CYCLOHEXEN-1-YL AND 2,6,6-TRIMETHYL-1,3,-CYCLOHEXADIEN-1-YL, SAID R1 REPRESENTING A MEMBER OF THE GROUP CONSISTING OF HYDROGEN, OXO, HYDROXY AND LOWER ALKANOYLOXY, AND SAID R2 REPRESENTING A MEMBER OF T HE GROUP CONSISTING OF HYDROGEN, HYDROXY AND LOWER ALKANOYLOXY, TO PRODUCE A MEMBER OF THE GROUP CONSISTING OF 1,18-DI-R-3,7,12,16TETRAMETHYL - 4,6,6,13,15 - HEXA - LOWERALKOXY - 2,7,9, 11,16 - OCTADECAPENTAENE AND 1,18 - DI-R-3,7,12,16-TETRAMETHYL - 4,6,6,13,13,15 - HEXA - LOWERALKOXY -2,7,11,16OCTADECATETRAEN-9-YNE WHEREIN R HAS THE SAME SIGNIFICANCE DEFINED ABOVE, HYDROLYZING AND DEALCOHOLIZING THE PRODUCT THUS OBTAINED IN THE PRESENCE OF ACID TO PRODUCE A MEMBER OF THE GROUP CONSISTING OF 1,18-DI-R-3,7,12,16TETRAMETHYL - 2,4,7,9,11,14,16 - OCTADECAHEPTAENE - 6,13DIONE AND 1,18-DI-R-3,7,12,16-TETRAMETHYL-2,4,7,11,14,16OCTADECAHEXAEN-9-YNE-6,13 -DIONE, WHEREIN R HAS THE SAME SIGNIFICANCE DEFINED ABOVE, CATALYTICALLY REDUCING THE 6,13DIONE THUS OBTAINED TO THE CORRESPONDING 6,13-DIOL AND DEHYDRATING THE 6,13-DIOL WITH ACID WHEREBY TWO MOLECULES OF WATER ARE SPLIT OFF WITH CONCOMMITANT ALLYL REARRANGEMENT. 